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STAY OPTIMAL

An Insider’s Guide to Your


Patients’ Blood Biomarkers
Introduction

As medical practitioners, how can we best provide


our patients with insight into their health? If
we’re to do this in a truly valuable way, then our
focus can’t merely lie on our patients’ illnesses
and conditions — patients want more than just a
diagnosis.

We need to offer guidance on the overall state of


our patients’ health, what conditions they are at
risk for, and what actionable steps they can take to
assist them in their journey toward optimal health.

This principle lies at the core of Functional


Medicine. One of the most effective ways that
practitioners can exercise this idea is through
testing for their patients’ blood biomarkers.

Blood biomarkers offer a window into the


body’s complex functions, and when examined
via functional analysis, these same biomarkers
provide a comprehensive and contextual roadmap
of your patient’s health.

Tracking biomarker changes over time will help


you provide answers and insights into your
patients’ health — enabling them to live a more
optimal life.

Learn more about OptimalDX >


How to use this guide

Blood testing can present an overwhelming array


of biomarkers that may serve as direct indicators
of your patient’s health, as indirect clues toward
the root of the problem, or even as red herrings.

This guide offers an overview of the most


significant biomarkers associated with major
systems in the body to help clarify the results of
blood testing. You can skip ahead to the sections
that seem most relevant to you, bookmark it to
return to key sections later, or read through the
guide in its entirety to gain a broad understanding
of what the different biomarkers in a blood test
may signify.

Each section discusses significant biomarkers in


depth and what their increased or decreased levels
may signify. These sections also include a list of
additional, but less-significant biomarkers that may
prove useful when assessing your patient’s health.

Finally, we’ve included a section at the end of this


guide labeled “Additional support for practitioners”
that discusses useful tools and training to assist
in measuring and tracking these biomarkers and
supporting your efforts toward maintaining your
patients’ optimal health.
Limits of Liability &
Disclaimer of Warranty

We have designed this book to provide information


regarding the subject matter covered. It is made
available with the understanding that the authors/
publishers are not liable for the misconception or
misuse of information provided.

The purpose of this book is to educate. It is


not meant to be a comprehensive source for
the topic covered and is not intended as a
substitute for medical diagnosis or treatment or
intended as a substitute for medical counseling.
Information contained in this book should not be
construed as a claim or representation that any
treatment, process or interpretation mentioned
constitutes a cure, palliative, or ameliorative. The
information covered is intended to supplement the
practitioner’s knowledge of their patient. It should
be considered as adjunctive support to other
diagnostic medical procedures.

This material contains elements protected under


International and Federal Copyright laws and
treaties. Any unauthorized reprint or use of this
material is prohibited.

Copyright © Weatherby & Associates, LLC


Table of Contents
Click any item below to jump to the section.

6 BLOOD SUGAR REGULATION & ENERGY


8 ELECTROLYTES & ACID-BASE BALANCE
10 ENZYMES
11 RED BLOOD CELL HEALTH & OXYGENATION
13 METABOLIC HEALTH
14 ADRENAL HEALTH
16 SEX HORMONE HEALTH: MALE & FEMALE
18 INFLAMMATION & OXIDATION
20 IRON
22 KIDNEY & PROSTATE HEALTH
24 CARDIOMETABOLIC HEALTH
27 HEPATOBILIARY HEALTH
29 MINERAL STATUS
31 VITAMIN STATUS
33 GASTROINTESTINAL FUNCTION
35 THYROID HEALTH
37 IMMUNE HEALTH
39 ADDITIONAL SUPPORT FOR PRACTITIONERS
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Blood Sugar Regulation & Energy


These biomarkers can keep you informed of the functional health of your patient’s
blood sugar regulation. By measuring these biomarkers, you can see whether there
is a growing trend towards hypoglycemia, metabolic syndrome, or insulin resistance.
If left unassessed and untreated, long-standing blood sugar dysregulation may lead
to hyperinsulinemia or type 2 diabetes.

GLUCOSE
Blood glucose levels are regulated by several important hormones, including insulin
and glucagon. Glucose is directly formed in the body from carbohydrate digestion
and by the conversion of other sugars, such as fructose, and fats in the liver.

Increased blood glucose levels are associated with types 1 and 2 diabetes,


metabolic syndrome, and insulin resistance.

Decreased blood glucose levels are associated with hypoglycemia.

HEMOGLOBIN A1C
Hemoglobin A1C, also known as glycohemoglobin, is formed when glucose and
hemoglobin combine over the course of a red blood cell’s lifespan, which lasts about
120 days. The amount of glycohemoglobin formed is in direct proportion to the
amount of glucose present in the bloodstream during this 120-day lifespan.

In the presence of high blood glucose levels (hyperglycemia), the amount


of hemoglobin that is converted into glycohemoglobin increases, and a
patient’s hemoglobin A1C levels will be high.

Hemoglobin A1C is used primarily to monitor long-term blood glucose control


and to help determine therapeutic options for treatment and management. The
closer hemoglobin A1C levels are kept to normal, the less likely those patients are to
develop the long-term complications of diabetes.

INSULIN: FASTING
Insulin is the hormone released in response to rising blood glucose levels and
decreases blood glucose by transporting glucose into the cells. Often, people lose
their ability to use insulin to effectively drive blood glucose into energy-producing
cells. This is commonly known as insulin resistance and is associated with increased
levels of insulin in the blood. Excess insulin is associated with greater risks of:

Heart attack | Stroke | Metabolic syndrome | Diabetes

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ADDITIONAL BIOMARKERS

In addition to the above, the following biomarkers and biomarker ratios can provide
insight into your patient’s blood sugar and energy regulation:

Estimated average glucose (eAG)


C-Peptide
Fructosamine
GlycoMark, or 1,5-anhydroglucitol
Adiponectin
ALT:AST ratio

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Electrolytes & Acid-Base Balance


An electrolyte imbalance can affect the body’s acid-base system, hydration, and even
the movement of ions across the cell membrane. Symptomatically, an electrolyte
balance can show up as:

Low blood pressure


Cold hands or feet
Poor circulation
Swelling in the ankles
Immune insufficiency

CHLORIDE
Chloride plays an important role in human physiology by regulating the acid-base
balance in the body. The amount of serum chloride is carefully regulated by the
kidneys.

Increased chloride levels are associated with metabolic acidosis.

Decreased chloride levels are associated with metabolic alkalosis.

Chloride is an important molecule in the production of hydrochloric acid in the


stomach — as a result, decreased levels of serum chloride are associated with
hypochlorhydria, or low stomach acid levels.

CARBON DIOXIDE (CO2 OR BICARBONATE)


The CO2 component of bicarbonate (HCO3, a byproduct of the body’s metabolism)
is available for acid-base balancing. Bicarbonate neutralizes metabolic acids in the
body.

Increased CO2 levels are associated with metabolic alkalosis and


hypochlorhydria.

Decreased CO2 levels are associated with metabolic acidosis.

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POTASSIUM
Potassium is one of the main electrolytes in the body. It plays an essential role in:

Nerve conduction
The maintenance of osmotic pressure
Muscle function
Cellular transport via the sodium-potassium pump
Acid-base balance

The majority of potassium in the body is intracellular. However, because of


potassium’s critical functions in human metabolism and physiology, it is essential for
the body to maintain optimal serum levels even though only a small concentration is
found outside of the cell. Additionally, potassium concentration is greatly influenced
by adrenal hormones. As such, potassium levels can be a marker for adrenal
dysfunction in addition to acid-base balance and general electrolyte status.

SODIUM
Sodium plays an important role as a blood electrolyte. It constitutes 90% of
electrolytes in the extracellular fluid, where it is the most prevalent cation. Sodium
functions to maintain osmotic pressure and acid-base balance and aids in nerve
impulse transmission and renal, cardiac, and adrenal functions. Sodium serves as a
general marker for acid-base balance and electrolyte status.

Increased sodium levels are most often due to dehydration (sweating, diarrhea,


vomiting, polyuria, etc.) or adrenal stress.

Decreased sodium levels are associated with adrenal insufficiency and edema.

ANION GAP
The anion gap is the measurement of the difference between the sum of the serum
cations (sodium and potassium) and the sum of the serum anions (CO2/bicarbonate
and chloride). The difference between these two reflects the concentrations of other,
unmeasured extracellular anions, such as phosphates, sulfates, ketones, proteins,
and lactic acid. An increase in these unmeasured anions is associated with acidosis
and thiamine deficiency.

ADDITIONAL BIOMARKERS
In addition to the above, the sodium:potassium ratio can assist you in assessing your
patients’ functional health.

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Enzymes
These enzyme biomarkers have traditionally been the go-to biomarkers for
assessing and diagnosing acute pancreatitis and/or damage to the pancreas itself.
From a more functional perspective, we can look at these enzyme biomarkers to
aid in the detection of pancreatic inflammation, pancreatic insufficiency, and
hepatobiliary dysfunction.

AMYLASE
Amylase converts starch into sugar and is produced primarily in the salivary glands
and pancreas.

Increased amylase levels  are seen with inflammation of the pancreas


(pancreatitis) or salivary glands.

Decreased amylase levels are seen with pancreatic insufficiency, a dysfunction


of the pancreas leading to a decreased output of pancreatic enzymes.

LIPASE
Lipase is produced primarily in the pancreas and supports the body in fat digestion.

Increased lipase levels are seen with inflammation of the pancreas (pancreatitis)


and gallbladder dysfunction.

Decreased lipase levels may be seen with pancreatic insufficiency.

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Red Blood Cell Health & Oxygenation


The following biomarkers are primarily helpful for assessing the degree of anemia
in your patient, a condition in which there are not enough healthy red blood cells to
carry oxygen around to the tissues of the body. Knowing that your patient is anemic
is not enough; you need to know the cause of the anemia.

Commonly, nutritional deficiencies are the culprit behind anemia, especially iron
and vitamin B12, but you must also rule out other causes that are not nutrition-
related. The biomarkers listed below can help you in this task, as well as the nutrient
biomarkers covered elsewhere in this guide.

RED BLOOD CELL COUNT


A red blood cell count determines the total number of red blood cells, or
erythrocytes, found in a cubic millimeter of blood. The red blood cell carries oxygen
from the lungs to the body tissues and transfers carbon dioxide from the tissues to
the lungs, where it is expelled.

Increased red blood cell levels are associated with dehydration, stress, a need
for vitamin C, and respiratory distress such as asthma.

Decreased red blood cell levels are primarily associated with anemia.

HEMATOCRIT
The hematocrit represents the percentage of a known volume of centrifuged blood
that consists of red blood cells.

Increased hematocrit levels  are associated with dehydration. This is also


associated with, but by no means diagnostic of, asthma or emphysema. Because
the blood is insufficiently oxygenated under these conditions, the body will
increase the red blood cell count to increase the number of cells that can be
oxygenated. The hematocrit will go up accordingly.

Decreased hematocrit levels are associated with anemia, though observing


decreased levels of hematocrit alone can’t tell you much about the cause and
type of anemia. The hematocrit should be evaluated with the other biomarkers
on a complete blood count/hematology panel to learn more.

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HEMOGLOBIN
Hemoglobin carries oxygen in red blood cells. The oxygen-combining capacity of the
blood is directly proportional to the hemoglobin concentration.

Increased hemoglobin levels are associated with dehydration.

Decreased hemoglobin levels  are associated with anemia. Measuring


hemoglobin is useful to determine the cause and type of anemia and for
evaluating the efficacy of anemia treatment.

ADDITIONAL BIOMARKERS
These additional biomarkers can provide you insight into your patient’s functional
health as well:

Mean corpuscular volume (MCV) Red cell distribution width (RDW)


Mean corpuscular hemoglobin (MCH) Platelets
Mean corpuscular hemoglobin Mean platelet volume (MPV)
concentration (MCHC)

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Metabolic Health
The metabolic health biomarkers are helpful for assessing systems in the body
associated with energy, strength, endurance, and overall performance.

CREATININE KINASE (CPK)


Creatine kinase (CPK) is a group of enzymes found in skeletal muscle, the brain,
and the heart muscle. Damage to one or more of these tissues will liberate CPK into
the serum, thus raising serum levels. CPK catalyzes the breakdown of adenosine
triphosphate (ATP) into adenosine diphosphate (ADP), a process that liberates high-
energy phosphate for metabolic processes such as muscle contraction.

Increased CPK levels  are associated with muscle damage or breakdown,


damage to the heart muscle as in an acute heart attack, heavy exercise, and brain
damage or inflammation. As levels of CPK increase, your patients may notice a
negative shift in recovery time as well as impairment in endurance and overall
performance indicators.

Decreased CPK levels may be seen in chronic muscle atrophy.

URIC ACID
Uric acid is produced as an end-product of purine, nucleic acid, and nucleoprotein
metabolism. Levels can increase due to overproduction by the body or decreased
excretion by the kidneys.

Increased uric acid levels are associated with gout, atherosclerosis, oxidative


stress, arthritis, kidney dysfunction, circulatory disorders, and intestinal
permeability.

Decreased uric acid levels  are associated with detoxification issues,


molybdenum deficiency, B12/folate anemia, and copper deficiency.
The typical focus of uric acid measurement is to assess the risk for gout, renal
failure, and leukemia. However, this marker is also a strong indicator of potential
inflammation and metabolic disturbance in the body.

ADDITIONAL BIOMARKERS
These additional biomarkers can be helpful in assessing your patients’ metabolic
health as well: Parathyroid hormone (PTH); Leptin

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Adrenal Health
The following biomarkers are helpful for assessing the functional health of your
patient’s adrenal glands.

The adrenal glands produce the glucocorticoid and mineralcorticoid hormones in


response to stress, resulting in “the fight or flight” response.

Unfortunately, when the body is under constant stress — which is quite common —
the adrenal glands become less functional. Adrenal dysfunction can be caused by an
increased output of stress hormones (adrenal hyperfunction) or, more commonly, a
decreased output of adrenal hormones (adrenal hypofunction).

DEHYDROEPIANDROSTERONE SULFATE (DHEA-S)


DHEA is produced primarily from the adrenal glands.

As the most abundant circulating steroid in the human body, DHEA influences more
than 150 known anabolic repair functions throughout the body and brain.

Additionally, DHEA is the precursor for the sex hormones: testosterone,


progesterone, and estrogen. DHEA-sulfate (DHEA-s) is the form of DHEA that we
measure in the blood to give us a sense of DHEA levels in the body.

Increased DHEA-S levels  may be associated with adrenal hyperplasia, a


condition that impairs the ability of the adrenal glands to produce cortisol and
other glucocorticoids.

Decreased DHEA-S levels  are associated with adrenal insufficiency and


many common age-related conditions, including diseases of the nervous,
cardiovascular, and immune systems. These include metabolic syndrome,
coronary artery disease, osteoporosis, mood disorders, and sexual dysfunction.

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CORTISOL
Cortisol is the most prominent glucocorticosteroid in the body and is essential for
the maintenance of several body functions, including:

Controlling blood sugar balance


Regulating metabolism
Reducing inflammation
Controlling blood pressure

Like other glucocorticosteroids, cortisol is synthesized from the common precursor


cholesterol in the adrenal glands. A serum cortisol test is used to identify dysfunction
in the adrenal gland, such as adrenal hyperfunction or hypofunction.

Additionally, it can be used to monitor Cushing’s Syndrome, a condition marked by


an overproduction of cortisol, and Addison’s Disease, a disease in which the adrenal
glands do not produce enough cortisol.

ADDITIONAL BIOMARKERS
The following biomarkers and biomarker ratios also play a role in assessing your
patient’s functional health:

Potassium
Sodium
Sodium:potassium ratio

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Sex Hormone Health – Male & Female


The blood levels of these crucial hormones diminish with age, contributing to age-
related dysfunctions, such as low libido, blood sugar problems, excess weight, heart
disease, and more.

ESTRADIOL
Estradiol (E2) is one of the most frequently measured estrogens, the others being
estrone (E1) and estriol (E3).

In women, low levels of estradiol can be a risk factor for osteoporosis and bone
fracture. Estrogen hormone therapy may improve menopausal women’s quality
of life. Increased levels of estradiol in women suggest an increased risk of breast
or endometrial cancer.

In men, estradiol is a minor hormone that plays a role in male sex hormone
physiology and is synthesized from testosterone and androstenedione. Low
levels of estradiol in men affect bone density, raising men’s risk for fractures as
their estradiol level decreases.

High levels of estradiol in men are associated with abdominal obesity, an


increased risk of cardiovascular disease, insulin sensitivity, and blood sugar
dysregulation.

TESTOSTERONE — TOTAL
Total testosterone levels encompass both the testosterone that is bound to serum
proteins and the unbound form (or free testosterone). Testosterone is the primary
sex hormone for men, but it also plays an important role in females as well.

In men, total testosterone levels are useful for assessing gonadal, adrenal, and
pituitary function.

In women, total testosterone levels can help in the evaluation of polycystic


ovarian syndrome, testosterone-producing tumors of the ovary, tumors of the
adrenal cortices, and congenital adrenal hyperplasia.

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TESTOSTERONE — FREE
Free testosterone is unbound to serum proteins such as sex hormone–binding
globulin (SHBG) or albumin.

In men, elevated free testosterone levels may be seen in patients that are
overusing supplemental testosterone, or it can be a sign of testosterone
overproduction in the body.

Decreased free testosterone levels in men are associated with several


dysfunctions, including metabolic syndrome, an increased risk of cardiovascular
disease, an increase in abdominal obesity, decreased libido, and erectile
dysfunction.

In women, elevated free testosterone levels are associated with excessive


growth of hair on the face and chest (hirsutism), polycystic ovary syndrome, and
an increased risk for insulin resistance. In women, low free testosterone levels
have been linked to an increased risk for osteoporosis, decreased lean body
mass, and decreased libido.

ADDITIONAL BIOMARKERS
These additional biomarkers allow you to do a more detailed analysis of your
patient’s sex hormone regulation:

SHBG
Follicle-stimulating hormone (FSH)
Luteinizing hormone (LH)
Pregnenolone
Progesterone
Testosterone — bioavailable
Testosterone — % free
Testosterone — % bioavailable
Prolactin
Insulin growth factor-1 (IGF-1)

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Inflammation & Oxidation


These biomarkers are helpful for assessing the degree of oxidative stress and
inflammation that your patient may be dealing with. Several biomarkers in the blood
increase in the presence of dysfunctions and diseases associated with inflammation
— cardiovascular disease, diabetes, hypertension, autoimmune diseases, and
fibromyalgia, to name a few.

Oxidative stress arises when the levels of free radicals in the body are high and/or
the levels of antioxidants in the body are low. The primary contribution to increased
free radicals is the exposure to toxins from our environment. When this occurs, you
may see shifts in the following biomarkers.

C-REACTIVE PROTEIN (CRP) & HIGH-SENSITIVITY (HS) CRP


C-reactive protein (CRP) is produced in the liver, primarily in response to increased
levels of a pro-inflammatory molecule, interleukin 6. CRP levels can increase with:

Infections
Abdominal obesity
Periodontal disease
Smoking
High blood pressure

High-sensitivity C-reactive protein (Hs-CRP) is a more sensitive CRP biomarker


that can help indicate the level of chronic inflammation in the body. Increased
Hs-CRP levels are associated with an increased risk of generalized inflammation,
cardiovascular disease, stroke, and diabetes.

FIBRINOGEN
Fibrinogen is one of the principal blood clotting proteins. It is produced in the liver,
and liver disease and dysfunction can cause a decrease in the level of circulating
fibrinogen. Levels increase with tissue inflammation or tissue destruction.

Increased fibrinogen levels are associated with an increased risk of cardiovascular


disease, heart attack, and stroke. Fibrinogen levels are often elevated in patients
suffering from cancer, especially colon cancer.

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HOMOCYSTEINE
Homocysteine is a molecule formed from the incomplete metabolism of the amino
acid methionine. Deficiencies in vitamins B6, B12, and folate cause methionine to be
converted into homocysteine.

Homocysteine increases the risk of cardiovascular disease by causing damage to the


endothelial lining of the arteries, especially in the heart.

Increased homocysteine levels  are associated with an increased risk of


cardiovascular disease and stroke, as well as cancer, depression, and
inflammatory bowel disease.

Decreased homocysteine levels are associated with a decrease in the body’s


detoxification capacity and an increased risk of oxidative stress.

ADDITIONAL BIOMARKERS
These additional biomarkers may be useful when assessing your patients for
inflammation and oxidation:

Erythrocyte sedimentation rate (ESR)


C-reactive protein (quantitative)
Ferritin
Albumin
Uric acid

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Iron
The iron-related biomarkers are helpful for assessing issues related to both iron
deficiency and iron overload. Iron deficiency is the most common form of anemia
worldwide, and the biomarkers on an iron panel are essential for assessing the
degree of iron deficiency that is affecting your patient.

In addition to iron deficiency, the iron markers can be used to assess other disorders
of iron metabolism including hemochromatosis, sideroblastic anemia, thalassemia,
and anemia of chronic disease.

IRON — TOTAL
Serum iron reflects iron that is bound to serum proteins such as transferrin. Serum
iron levels will begin to fall somewhere between the depletion of the iron stores and
the development of anemia.

Increased iron levels are associated with liver dysfunction, conditions of iron


overload (hemochromatosis and hemosiderosis), and infections.

Decreased iron levels  are associated with iron deficiency anemia,


hypochlorhydria, and internal bleeding. The degree of iron deficiency is best
determined in the context of ferritin, TIBC, and % transferrin saturation levels.

FERRITIN
Ferritin is the main form of iron storage in the body.

Decreased ferritin levels are strongly associated with iron deficiency where it is


the most sensitive test to detect a growing trend towards iron deficiency.

Increased ferritin levels are associated with iron overload, an increasing risk of


cardiovascular disease, inflammation, and oxidative stress.

TOTAL IRON BINDING CAPACITY (TIBC)


Total iron binding capacity (TIBC) is an approximate estimation of the serum
transferrin level. The transferrin protein carries most of the iron in the blood.

Elevated TIBC levels are associated with iron deficiency anemia.

Decreased TIBC levels are associated with possible iron overload or a protein


deficiency.

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% TRANSFERRIN SATURATION
The % transferrin saturation index is a calculated value that tells how much serum
iron is bound to the iron-carrying protein transferrin. A % transferrin saturation
value of 15% means that 15% of iron-binding sites of transferrin is being occupied by
iron.

Increased % transferrin saturation levels function as a sign of too much iron in


the blood or iron overload.

Decreased % transferrin saturation levels serve as a sensitive screening test for


iron deficiency anemia.

ADDITIONAL BIOMARKERS
These additional biomarkers may be useful when assessing the functional health of
your patients:

Transferrin
Unsaturated iron-binding capacity (UIBC)

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Kidney & Prostate Health


Measure these biomarkers in order to assess the functional health of your patient’s
renal function and prostate. A decrease in renal function in your patient can be due
factors such as dehydration, heavy metal toxicity, over the counter or prescription
drugs, renal insufficiency, liver dysfunction, or renal disease.

Shifts in these biomarkers may also indicate that your patient’s prostate function
needs further assessment. Consider conditions such as benign prostatic
hypertrophy, prostatitis, urinary tract infection, or early-stage prostate cancer.

A close review of prostate-specific antigen (PSA) levels and further testing for
prostatic function may be required.

BLOOD UREA NITROGEN (BUN)


BUN, or blood urea nitrogen, is used predominantly to measure kidney function.
BUN reflects the ratio between the production and clearance of urea in the body.
Urea is formed almost entirely by the liver from both protein metabolism and
protein digestion. The amount of urea excreted as BUN varies with the amount of
dietary protein intake.

Increased BUN levels are a sign of kidney dysfunction. An increased BUN level


may be due to increased production of urea by the liver or decreased excretion
by the kidney. Increased BUN levels are also associated with dehydration and
hypochlorhydria.

Decreased BUN levels are associated with malabsorption and a diet low in


protein.

CREATININE
Creatinine is produced primarily from the contraction of muscles and is removed by
the kidneys. A disorder of the kidney and/or urinary tract will reduce the excretion
of creatinine and thus raise blood serum levels. Creatinine is traditionally used with
BUN to assess for impaired renal function.

Increased creatinine levels are associated with kidney dysfunction, kidney


disease and a possible dysfunction in the prostate.

Decreased creatinine levels  are associated with muscle atrophy due to


creatinine’s connection to muscle metabolism.

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TOTAL PROSTATIC SPECIFIC ANTIGEN (PSA — TOTAL)


PSA is the most abundant protein synthesized in the prostate gland. Total PSA is
used as a biological marker to detect diseases related to the prostate.

Increased PSA levels are associated with an enlarged prostate (benign prostatic


hyperplasia — BPH), prostate inflammation (prostatitis), and prostate cancer.

It’s important to remember that elevated levels of total PSA may not necessarily
signal prostate cancer, and prostate cancer may not always be accompanied by an
expression of PSA.

ADDITIONAL BIOMARKERS
A more thorough analysis of the kidney and prostate can be made by assessing the
optimal levels of the following biomarkers and biomarker ratios:

BUN:creatinine ratio
Estimated glomerular filtration rate (eGFR)
Creatinine clearance

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Cardiometabolic Health
Measuring these biomarkers will be helpful for assessing your patient’s risk for
developing cardiovascular disease. Cardiovascular disease is still the number
one killer of men and women in the world, and heart disease is a major cause of
morbidity in our aging population.

Unfortunately, most heart disease is silent and asymptomatic, so a thorough


assessment of the body’s cardiometabolic system must include the following
biomarkers as well as the additional biomarkers listed below.

TRIGLYCERIDES
Serum triglycerides are composed of fatty acid molecules that enter the bloodstream
either from the liver or from the diet. Patients that are optimally metabolizing their
fats and carbohydrates tend to have a triglyceride level at about one-half of the total
cholesterol level.

Levels will be elevated in patients with metabolic syndrome; fatty liver disease;
and in patients with an increased risk of cardiovascular disease, hypothyroidism,
and adrenal dysfunction.

Levels will be decreased in patients with liver dysfunction, a diet deficient in fat,
and inflammation.

CHOLESTEROL – TOTAL
Cholesterol is a steroid found in every cell of the body and in the plasma. It is an
essential component in the structure of the cell membrane, where it controls
membrane fluidity.

Additionally, it provides the structural backbone for every steroid hormone in the
body, which includes adrenal and sex hormones and vitamin D. The myelin sheaths
of nerve fibers are also derived from cholesterol, and the bile salts that emulsify fats
are composed of cholesterol.

The liver, the intestines, and the skin produce between 60%–80% of the body’s
cholesterol. The remainder comes from diet.

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Increased cholesterol levels are just one of many independent risk factors


for cardiovascular disease. It is also associated with metabolic syndrome,
hypothyroidism, biliary stasis, and fatty liver disease.

Decreased cholesterol levels are a strong indicator of gallbladder dysfunction,


oxidative stress, inflammatory process, and low-fat diets.

It’s important to remember that elevated levels of total PSA may not necessarily
signal prostate cancer, and prostate cancer may not always be accompanied by an
expression of PSA.

LOW-DENSITY LIPOPROTEIN (LDL)


LDL transports cholesterol and other fatty acids from the liver to the peripheral
tissues for uptake and metabolism by the cells. It is known as “bad cholesterol”
because it is thought that this process of bringing cholesterol from the liver to the
peripheral tissue increases the risk for atherosclerosis.

Increased LDL levels are just one of many independent risk factors for cardiovascular
disease. Increased levels are also associated with metabolic syndrome, oxidative
stress, and fatty liver.

HIGH-DENSITY LIPOPROTEIN (HDL)


HDL transports cholesterol from the peripheral tissues and vessel walls to the liver
for processing and metabolism into bile salts. Unlike LDL, HDL is often referred to as
“good cholesterol” — it is thought that the process of bringing cholesterol from the
peripheral tissue to the liver protects against atherosclerosis.

Decreased HDL levels are considered atherogenic.

Increased HDL levels are considered to protect against atherosclerosis.

LIPOPROTEIN (A)
Lipoprotein (a), or Lp(a), is a small, dense lipoprotein that carries cholesterol in
the blood. Increased Lp(a) levels are considered an independent risk factor for
atherosclerosis and may be a strong indicator of early cardiovascular disease.

There are no known negative effects of levels of Lp(a) at the lower end of the
reference range. Some individuals may even have no detectable Lp(a) in their blood.

25 CONTACT AN EXPERT CARDIOMETABOLIC HEALTH


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ADDITIONAL BIOMARKERS
These additional biomarkers and biomarker ratios will allow you to conduct a more
detailed analysis of your patient’s cardiometabolic system:

LDL:HDL ratio
Cholesterol:HDL ratio
Triglyceride:HDL ratio
Very low density lipoprotein (VLDL)
Apolipoprotein-A1
Apolipoprotein B
Apo B:Apo A-1 ratio
Lipoprotein-associated phospholipase-A2 (LP pla2)
Nuclear magnetic resonance (NMR) lipoprofile
Vitamin D
Glucose
Insulin
HsCRP
Fibrinogen
Ferritin
Estradiol
Testosterone
Homocysteine

26 CONTACT AN EXPERT CARDIOMETABOLIC HEALTH


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Hepatobiliary Health
With these biomarkers, you can assess the functional health of your patient’s liver
and gallbladder. Factors affecting liver function include fatty liver disease (steatosis),
hepatitis (inflammation of the hepatic cells from infections, toxins, etc.), liver cell
damage (from cirrhosis, infection, alcohol, chemical damage, and hepatic necrosis),
or a decrease in either the phase 1 or phase 2 liver detoxification pathways.

Factors affecting gallbladder function include problems in the liver itself that
compromises the production of bile (biliary insufficiency), the progressive thickening
of the bile within the gallbladder (biliary stasis), or biliary obstruction, which causes
cholestasis, a condition characterized by impaired bile flow.

ALANINE TRANSAMINASE (ALT)


Alanine transaminase (ALT) is an enzyme present in high concentrations in the liver
and, to a lesser extent, in the skeletal muscle, the heart, and kidney. ALT will be
liberated into the bloodstream following cell damage or destruction.

Any condition or circumstance that causes damage to the hepatocytes will leak ALT
into the bloodstream. These include exposure to chemicals, viruses (viral hepatitis,
mononucleosis, cytomegalovirus, Epstein Barr, etc.), or alcoholic hepatitis.

Increased ALT levels are associated with steatosis (fatty liver disease), cirrhosis,
and hepatitis.

Decreased ALT levels are associated with a B6 deficiency.

ASPARTATE AMINOTRANSFERASE (AST)


Aspartate Aminotransferase (AST) is an enzyme present in highly metabolic tissues
such as skeletal muscle, the liver, the heart, kidney, and lungs. This enzyme is
released into the bloodstream following cell damage or destruction.

Increased AST levels occur when liver cells and/or heart muscle cells and/
or skeletal muscle cells are damaged. The cause of the damage must be
investigated.

Decreased AST levels are associated with a B6 deficiency.

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GAMMA GLUTAMYL TRANSFERASE (GGT)


Gamma glutamyl transferase (GGT) is an enzyme that is present in the highest
amounts in the liver cells and to a lesser extent the kidney, prostate, and pancreas. It
is also found in the epithelial cells of the biliary tract.

Increased GGT levels are associated with biliary insufficiency, biliary stasis


and biliary obstruction. Levels can also be increased following chronic alcohol
consumption.

Decreased GGT levels are associated with vitamin B6 and magnesium deficiency.

BILIRUBIN — TOTAL
Total bilirubin is composed of two forms of bilirubin: indirect, or unconjugated
bilirubin, which circulates in the blood on its way to the liver; and direct, or
conjugated bilirubin, which is the form of bilirubin made water-soluble before it is
excreted in the bile.

Increased total biliirubin levels are associated with a dysfunction or blockage of


the liver, gallbladder, or biliary tree, or red blood cell hemolysis.

Decreased total bilirubin levels are associated with an increase in oxidative


stress.

ADDITIONAL BIOMARKERS
These additional biomarkers and biomarker ratios allow you to do a more detailed
analysis of your patient’s hepatobiliary system:

Bilirubin — Direct
Bilirubin — Indirect
AST:ALT ratio
Alkaline phosphatase (Alk phos)
Lactate dehydrogenase (LDH)

28 CONTACT AN EXPERT HEPATOBILIARY HEALTH


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Mineral Status
These biomarkers can provide us with a general indication of the balance of certain
minerals in the body.

Mineral levels in the body are closely regulated, and deficiencies in one or more
minerals may be due to a number of factors, such as the amount of a given mineral
in the diet; a patient’s ability to digest and break down individual minerals from
food or supplements; and how well those minerals are absorbed, transported, and
ultimately taken up by the cells themselves.

MAGNESIUM — SERUM AND RED BLOOD CELL


Magnesium is important for many different enzymatic reactions, including
carbohydrate metabolism, protein synthesis, nucleic acid synthesis, and muscular
contraction. Magnesium is also needed for energy production and is used by the
body in blood clotting.

Increased serum or red blood cell magnesium levels are mainly associated with
kidney dysfunction and renal failure.

Decreased serum or red blood cell magnesium levels are a sign of magnesium


deficiency and is a common finding with muscle cramps.

CALCIUM
Serum calcium levels, which the body tightly regulates within a narrow range, are
principally regulated by parathyroid hormone (PTH) and vitamin D.

Increased calcium levels  are associated with parathyroid hyperfunction. If


calcium is significantly elevated, check serum PTH levels and refer to an
endocrinologist.

Decreased calcium calcium levels indicate that calcium regulation is out of


balance and not necessarily that the body is deficient of calcium and needs
supplementation. Before supplementing with calcium, check vitamins A, B, C,
and D levels; rule out hypochlorhydria; and the need for magnesium,
phosphorus, unsaturated fatty acids, and iodine as some of the reasons for a
calcium “need” before supplementing with calcium.

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ZINC – SERUM
Zinc is a trace mineral that participates in a significant number of metabolic
functions and is found throughout the body’s tissues and fluids.

Increased zinc levels are often seen in people supplementing with zinc.

Decreased zinc levels are associated with zinc deficiency. Zinc deficiency will
negatively affect the multitude of metabolic functions that depend on zinc,
including wound healing, immune function, protein synthesis, carbohydrate and
lipid metabolism, antioxidant activity, and the production of insulin and thyroid
hormone.

ADDITIONAL BIOMARKERS
These additional biomarkers and biomarker ratios will allow you to do a more
detailed analysis of your patient’s mineral status:

Calcium:albumin ratio
Calcium:phosphorous ratio
Selenium — serum
Copper — serum
Zinc — red blood cell
Ceruloplasmin
Chromium

30 CONTACT AN EXPERT MINERAL STATUS


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Vitamin Status
Vitamin levels are constantly fluctuating based on a number of factors, such as the
amount a patient receives from their diet, a patient’s ability to digest and break down
individual vitamins from the food or supplements you consume, and the ability of
those vitamins to be absorbed, transported and taken up into the cells.

VITAMIN D (25-OH)
Testing for levels of 25-OH vitamin D is an exceptionally effective way to assess
vitamin D status. An increased serum vitamin D is usually seen with patients that
are supplementing with too much vitamin D.  A decreased serum vitamin D  is
extremely common and is a sign of vitamin D deficiency. Vitamin D deficiency has
been associated with many disorders including:

Several forms of cancer


Hypertension
Cardiovascular disease
Chronic inflammation
Chronic pain
Mental illness, including depression
Diabetes
Multiple sclerosis
And more

VITAMIN B12
Vitamin B12 is an essential nutrient for DNA synthesis and red blood cell maturation.
Additionally, B12 is necessary for myelin sheath formation and the maintenance of
nerves in the body.

Decreased serum B12 levels are associated with a deficiency of B12, insufficient


B12 intake in the diet, or malabsorption.

Paradoxically, increased serum B12 levels may be accompanied by signs of B12


deficiency and may indicate a functional deficiency marked by inadequate uptake
at the tissue level.

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ADDITIONAL BIOMARKERS
These additional biomarkers allow you to do a more detailed analysis of your
patient’s vitamin status:

Vitamin A
Vitamin C
Vitamin E
Active B12
Folate — serum
Folate — red blood cell
Methylmalonic acid

32 CONTACT AN EXPERT VITAMIN STATUS


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Gastrointestinal Function
Measuring these biomarkers can help you assess the functional status of your
patient’s gastrointestinal (GI) system. Factors affecting GI function include
inadequate chewing, eating when stressed or in a hurry, hypochlorhydria, gastritis,
pancreatic insufficiency, dysbiosis, and/or intestinal hyperpermeability.

PROTEIN — TOTAL
Total serum protein is made up of the levels of albumin and total globulin in the
blood. Conditions that affect albumin and total globulin readings will impact the total
protein value.

Decreased total protein levels can be an indication of malnutrition, digestive


dysfunction due to a need for hydrochloride, or liver dysfunction. Malnutrition
leads to a decreased total protein level in the serum primarily from lack of
available essential amino acids.

Increased total protein levels are most often due to dehydration.

ALBUMIN
Albumin is one of the major blood proteins. Produced primarily in the liver, albumin
plays a major role in water distribution and serves as a transport protein for
hormones and various drugs.

Decreased albumin levels  can be an indication of malnutrition, digestive


dysfunction due to HCl need (hypochlorhydria), or liver dysfunction. Malnutrition
leads to a decreased albumin level in the serum primarily from lack of available
essential amino acids. Decreased albumin can also be a strong indicator of liver
dysfunction, oxidative stress, and excess free radical activity.

Increased albumin levels are a strong indicator of dehydration.

33 CONTACT AN EXPERT GASTROINTESTINAL FUNCTION


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GLOBULIN — TOTAL
Total globulin is composed of individual globulin fractions known as the alpha 1,
alpha 2, beta, and gamma fractions. Total globulin levels are greatly impacted by
concomitant increases or decreases in one or more of these fractions.

Globulins constitute the body’s antibody system, and the total serum globulin is a
measurement of all the individual globulin fractions in the blood.

Increased total globulin levels  are associated with hypochlorhydria, liver


dysfunction, immune activation, oxidative stress, and inflammation.

Decreased levels are associated with inflammation in the digestive system and


immune insufficiency.

ADDITIONAL BIOMARKERS
These additional biomarkers and biomarker ratios may be helpful when assessing
your patients’ functional gastrointestinal health:

Gastrin
Albumin:globulin ratio

34 CONTACT AN EXPERT GASTROINTESTINAL FUNCTION


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Thyroid
Changes in these biomarkers may indicate that there is dysfunction in your patient’s
thyroid and a need for further assessment and treatment.

Consider that the dysfunction might be a hyperactive thyroid, primary


hypothyroidism (a dysfunction in the thyroid itself, often caused by autoimmune
thyroiditis), secondary hypothyroidism (a dysfunction in the anterior pituitary), or
thyroid conversion syndrome.

THYROID-STIMULATING HORMONE (TSH)


TSH, or thyroid-stimulating hormone, is a hormone produced by the anterior
pituitary to control the thyroid gland’s production of thyroxine (T4), to store T4, and
to release it into the bloodstream. TSH synthesis and secretion is regulated by the
release of TRH (thyroid releasing hormone) from the hypothalamus.

TSH levels represent the body’s need for more thyroid hormone (T4 or
triiodothyronine — T3), which relates to the body’s need for energy.

High TSH levels indicate that the body needs more thyroid hormone.

Low TSH levels reflect the body’s low need for thyroid hormone.

Optimal TSH levels in a normally functioning pituitary can tell us that the amount
of T4 in the blood matches the body’s current need and/or ability to utilize the
energy necessary for optimal cell function.

FREE THRYOXINE (T4)


T4 is the major hormone secreted by the thyroid gland. T4 production and secretion
from the thyroid gland are stimulated by TSH. Deficiencies of zinc; copper; and
vitamins A, B2, B3, B6, and C will cause a decrease in the production of T4 by the
follicles of the thyroid gland. Free T4 is the unbound form of T4 in the body.

Only about 0.03%–0.05% of circulating T4 is in its free form. Free T4 will be elevated
in hyperthyroidism and decreased in hypothyroidism.

35 CONTACT AN EXPERT THYROID


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FREE TRIDOTHYRONINE (T3)


T3 is the most active thyroid hormone and is primarily produced from the conversion
of T4 in the peripheral tissue. Free T3 is the unbound form of T3 measured in the
blood. Free T3 represents approximately 8%–10% of circulating T3 in the blood. Free
T3 levels may be elevated with hyperthyroidism and decreased with hypothyroidism.

ADDITIONAL BIOMARKERS
These additional biomarkers and biomarker ratios allow you to perform a more
detailed analysis of your patient’s thyroid health:

Total T4
Total T3
T3 uptake
Free thyroxine index
Reverse T3
Free T3:reverse T3 ratio
Thyroid-binding globulin
Thyroglobulin antibodies
Anti-thyroid peroxidase (anti-TPO) antibodies
Thyrotropin receptor antibodies
Thyroid-stimulating immunoglobulin

36 CONTACT AN EXPERT THYROID


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Immune Health
When the immune system is in a state of balance, we can cope with infections with
little or no lasting negative side-effects. The following biomarkers and the additional
biomarkers listed below allow you to determine whether your patient’s immune
system is in a state of balance or not.

Some of the factors to consider include immune insufficiency, bacterial or viral


infections, or GI dysfunction associated with decreased immune function. These
include abnormal immunity in the gut lining, a decrease in immune cell function in
the gut, or an increase in abnormal bacteria in the gut.

TOTAL WHITE BLOOD CELL COUNT


A total white blood cell (WBC) count measures the sum of all the WBCs in the
peripheral blood. WBCs fight infection; defend the body through a process called
phagocytosis; and produce, transport, and distribute antibodies as part of the
immune process.

It is important to look at the WBC differential count (which counts the different
varieties of WBCs: neutrophils, lymphocytes, etc.) to identify the source of an
increased or decreased WBC count.

Decreased total WBC levels  are associated with chronic bacterial or viral
infections, immune insufficiency, and may be seen in people eating a raw food
diet.

Increased total WBC levels are associated with acute bacterial or viral infections
and may be seen in people who eat a diet of highly refined foods.

NEUTROPHILS
Neutrophils are WBCs used by the body to combat bacterial infections and are the
most numerous and important white cell in the body’s reaction to inflammation.

Increased neutrophil levels will be seen in bacterial infections.

Decreased neutrophil levels are often seen in chronic viral infections.

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LYMPHOCYTES
Lymphocytes are WBCs that are part of the adaptive immune system. They are able
to recognize invading organisms using specific cellular receptors and are the source
of immunoglobulins, which function as antibodies.

Increased lymphocyte levels are usually a sign of a viral infection but can also be
a sign of increased toxicity in the body or inflammation.

Decreased lymphocyte levels are often seen in a chronic viral infection, for which
the body can use up a large number of lymphocytes and undergo significant
oxidative stress. A decreased lymphocyte count may also indicate the presence
of a fatigued immune response, especially with a low total WBC count.

MONOCYTES
Monocytes are WBCs that represent the body’s second line of defense against
infection. They are phagocytic cells that are capable of movement and remove dead
cells, microorganisms, and particulate matter from circulating blood. Levels tend to
rise during the recovery phase of an infection or with chronic infection.

ADDITIONAL BIOMARKERS
These biomarkers and biomarker ratios can also be useful in assessing your patients’
immune health:

Eosinophils
Basophils
Bands
Neutrophil:lymphocyte ratio

38 CONTACT AN EXPERT IMMUNE HEALTH


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